Delivery of therapeutic agent

Abstract

A method of producing nanovesicles comprising an oligonucleotide inhibitor to an oncogene or a proto-oncogene or the gene product thereof, said method comprises a) introducing a DNA sequence encoding an oligonucleotide capable of inhibiting a human oncogenic or proto-oncogenic transcription factor, into a mammalian cell; b) allowing the cell to express said inhibitor oligonucleotide; and c) obtaining nanovesicles containing said inhibitor oligonucleotide from said cell. Nanovesicles produced by the claimed method can be effectively and specifically targeted to e.g. cancer cells to deliver the inhibitor oligonucleotide.

Description

FIELD OF THE INVENTION[0001]The present invention relates to the delivery of potentially therapeutic agents via cell-derived vesicles.BACKGROUND OF THE INVENTION[0002]Cancer is a leading cause of death worldwide. In 2008, various cancers accounted for 7.6 million deaths (around 13% of all deaths), according to the World Health Organization (WHO), and this number is projected to continue rising, with an estimated 13.1 million deaths worldwide in 2030 [GLOBOCAN 2008 (IARC) Section of Cancer Information (Nov. 11, 2012)].[0003]Malignant melanoma is responsible for a majority of deaths caused by skin tumors, and is the most common malignancy in young adults. When melanoma is metastatic, prognosis is unfavorable, and the therapeutic alternatives are few. Uveal melanoma has different clinical features than skin melanomas, and often spreads primarily to liver. For uveal melanoma it has been proposed that approximately one out of two patients will develop metastases within 15 years after tre...

AI Technical Summary

Benefits of technology

The present invention is a method for producing nanovesicles that can be used for delivering inhibitory molecules to cancer cells. The method is advantageous compared to other methods because it can easily be scaled up and the nanovesicles produced can contain higher concentrations of inhibitor molecules. The method is also cost-effective and can be used to produce targeted nanovesicles. The invention provides a solution for the need for tissue-specific targeting of nanovesicles to cancer cells, which could fail with other targeting methods. The method may involve expressing targeting molecules on the surface of the nanovesicle-producing cells, which can interact with specific receptors on cancer cells. In some embodiments, the cell can express multiple targeting molecules to increase targeting specificity.

Problems solved by technology

Cancer is a leading cause of death worldwide.

When melanoma is metastatic, prognosis is unfavorable, and the therapeutic alternatives are few.

This approach is however very invasive and associated with risks of surgical complications.

Treatment of cancer is therefore one of the major challenges facing modern medicine.

A drawback of chemotherapeutic agents is that they are unselective and cause adverse side effects, which effectively limits dosage and hence also the therapeutic effect.

However this treatment only prolongs life with a few months in metastatic melanoma, and only works in those melanomas that have this specific mutation.

The downstream targets however lack enzymatic activity, and are often impossible to treat with small molecules, because of their tertiary structure.

Further, as a small molecule inhibitor would distribute throughout the body, it would also cause systemic side effects in normal, healthy cells that are depending on such downstream molecules.

However, a major challenge for the development of RNAi-based therapeutics and other gene therapy applications is delivery of the therapeutic agent (e.g. an RNA molecule).

Hence, one obstacle to successful targeting of genes and proteins involved in disease, including cancer, is the development of a safe and effective method of delivering the therapeutic agent to the target.